Joubert syndrome is characterized by episodic hyperpnea and apnea, developmental delay, hypotonia, truncal ataxia, ophthalmologic abnormalities, and vermian dysgenesis. We studied 15 patients with the diagnosis of Joubert syndrome to (1) more fully define the syndrome's clinical features, and (2) correlate the clinical features with magnetic resonance imaging (MRI) findings. Eight of 15 patients had a history of episodic hyperpnea and apnea. All patients had developmental delay and hypotonia. Of the 13 patients receiving detailed neuro-ophthalmologic evaluations, three had optic nerve dysplasia, pendular nystagmus, and gaze-holding nystagmus. All 13 patients had a normal vestibulo-ocular reflex based on head thrust, but had absent to poor ability to cancel the vestibulo-ocular reflex horizontally and vertically. Twelve of 13 patients had impaired smooth pursuit. Twelve of 13 patients had defects in initiation of saccades and quick phases. Two of the most consistent radiologic features were absent or hypoplastic posterior cerebellar vermis, and deformed midbrain and pontomesencephalic junction, which based on ocular motor physiology correlate with the vestibulo-ocular reflex cancellation/ pursuit defect and saccade initiation defect, respectively. As a result of midbrain, vermian, and superior cerebellar peduncle abnormalities, axial neuroimaging showed a unique "molar tooth" appearance of these structures. These results indicate that Joubert syndrome results from maldevelopment of the midbrain and cerebellar vermis, producing a pathognomonic sign on MRI.

In this highly heterogeneous population of children with congenital lactic acidosis, oral DCA for 6 months was well tolerated and blunted the postprandial increase in circulating lactate. However, it did not improve neurologic or other measures of clinical outcome.

Joubert syndrome is a rare autosomal-recessive condition characterized by early hyperpnea and apnea, developmental delay, and truncal ataxia. We previously described key ocular motor signs in Joubert syndrome and the molar tooth sign resulting from dysplasia of the isthmic segment of the brain stem, superior cerebellar peduncles, and vermis. In this study, we obtained clinical and developmental data in 61 cases, and radiologic data in 46 of these, to determine the prevalence of the molar tooth sign in a large sample, and to ensure that magnetic resonance images obtained for study were representative of the Joubert syndrome population at large. We studied the morphology of the isthmic segment of the pontomesencephalic junction, the segment of the brain stem derived from the primitive isthmus. Portions of the cerebellum analyzed included the superior cerebellar peduncles, the anterior and posterior lobes of the vermis, and the flocculonodular lobe. In one case, autopsy of the brain was performed. The average age at diagnosis was 33 months. All patients were hypotonic and developmentally delayed. The molar tooth sign was present in 85% of cases with 13% of these showing additional malformations. All patients without the molar tooth sign had other mimicking conditions such as neocerebellar dysgenesis, isolated vermian atrophy, cerebellar aplasia, and cystic dilation of the cisterna magna. Autopsy showed aplasia of the cerebellar vermis with dysplasia of the dentate nucleus, elongated locus coeruleus, and marked dysplasia of the caudal medulla. A better understanding of the clinical, radiologic, and pathologic features of Joubert syndrome should help uncover the genetic basis for the syndrome.

The histopathological, clinical, and radiological features of the intracranial cavernous angioma are reviewed, based on an analysis of 138 symptomatic, histologically verified cases. Twelve of the cases are from our own series and 126 were collected from appropriately documented reports in the modern literature. The analysis indicated that, at the time of diagnosis, one-third of the patients (49 cases) were being evaluated for seizures, one-third (40 cases) for clinical evidence of hemorrhage, and one-third (49 cases) for mass lesions. Unlike the other two groups, the group presenting with clinical evidence of hemorrhage was distinguished by a dominant age at the time of diagnosis (41% were diagnosed during the 4th decade of life), by a high incidence of prior neurological evaluation (43%), by a higher rate of diagnosis at autopsy (28%) than at operation, and by the absence of microscopic calcification within the lesion.

OBJECTIVE -Children who develop cerebral edema (CE) during diabetic ketoacidosis (DKA) exhibit definable signs and symptoms of neurological collapse early enough to allow intervention to prevent brain damage. Our objective was to develop a model for early detection of CE in children with DKA. RESEARCH DESIGN AND METHODS-A training sample of 26 occurrences of DKA complicated by severe CE and 69 episodes of uncomplicated DKA was reviewed. Signs of neurological disease were incorporated into a bedside evaluation protocol that was applied to an independent test sample of 17 patients previously reported to have developed symptomatic CE during treatment for DKA. Head computed tomograms and their reports were reviewed.RESULTS -The protocol allowed 92% sensitivity and 96% specificity for the recognition of CE sufficiently early for intervention. The diagnostic criteria were fulfilled in two temporal patterns, defining early-and late-onset CE. Although initial computed tomograms were often normal, the findings also included diffuse CE and focal brain injury, the latter only in patients with an early onset of abnormal neurological signs.CONCLUSIONS -CE may occur in the absence of acute changes on head computed tomograms. Early detection of CE at the bedside using an evidence-based protocol permits intervention in time to prevent permanent brain damage. Diabetes Care 27:1541-1546, 2004M ost children with diabetic ketoacidosis (DKA) exhibit abnormal neurological function. Therefore, evidence-based guidance for discerning the patients who require lifesaving intervention is needed. Cerebral dysfunction in DKA is usually a manifestation of metabolic derangement, but cerebral edema (CE) arises in ϳ1% of episodes and is a complication that frequently causes irreversible brain damage and death (1-7). Neurological collapse from CE is typically described as having sudden onset and progressing rapidly, with recovery depending on prompt reduction of intracranial pressure (4,8 -10). The object of this study was to delineate the signs and symptoms of neurological compromise that predict progression to severe CE in children with DKA.CE occurs rarely in patients older than age 20 years (8,11,12), despite the presence of asymptomatic CE in most adults and children with DKA (13-16). This age dependence may point to developmental changes in cerebral metabolism as critical elements in the pathogenesis of CE. For example, children's brains are reported to have higher fuel and oxygen requirements than those of adults (17,18). Hypoxia is further implicated because the brains of patients with DKA may extract blood oxygen less efficiently than healthy individuals (16) and the reported association of symptomatic CE with low partial pressures of carbon dioxide in arterial blood may reflect harmful cerebral vasoconstriction (5,6). Exuberant rehydration with hypotonic fluid and bicarbonate administration may aggravate the CE (5,6,9,11,12,19 -22); however, the evidence that CE is primarily iatrogenic is not compelling (6,8,(23)(24)(25)(26)(27)(28)(29)...

The presence of the empty delta sign on contrast material-enhanced computed tomographic (CT) scans of the brain is considered pathognomonic of sagittal sinus thrombosis (SST); however, a valid explanation for its appearance is lacking, despite several hypotheses. To determine the frequency of the sign and its prognostic significance, 76 reported cases (112 CT manifestations) of SST and SST-related intracranial sinovenous occlusive disease were reviewed. Ten CT signs related to both disease processes were reported; the empty delta sign was the most frequently reported sign (28.6%) of SST. Patients with hemorrhagic infarction and/or the empty delta sign on CT scans had the poorest prognosis. A case illustrative of the empty delta sign is described in which there was engorgement of endothelial- and nonendothelial-lined spaces in the dura mater with hemorrhagic rupture into the dural leaf. The empty delta sign can probably be explained on the basis of the rich dural venous collateral circulation, consisting primarily of lateral lacunae, a vascular mesh (dural cavernous spaces), and meningeal venous tributaries.

The clinical and anatomical features of 21 surgically treated saccular aneurysms of the posterior inferior cerebellar artery (PICA) are analyzed. Seventeen of these lesions originated from the PICA-vertebral junction, and four arose from distal PICA branching sites. Twelve lesions arose from the left PICA, nine were right-sided, and all were small (less than 12.5 mm). Most of these aneurysms occurred in females (16 of 21) and presented as classic subarachnoid hemorrhage. The lack of specific focal deficits prevented an accurate pre-angiographic determination of aneurysm location in most instances. Clinically significant vasospasm and aneurysm multiplicity occurred with approximately equal frequency as at other locations. The angiographic and surgical features of these lesions are determined by the course of the vertebral artery and PICA; that is, they occur at branching sites and at curves in the parent vessel, and point in the direction in which flow would have continued if the curve at the aneurysm's origin had not been present. Aneurysms at the PICA-vertebral junction usualthese lesions are determined by the course of the vertebral artery and PICA; that is, they occur at branching sites and at curves in the parent vessel, and point in the direction in which flow would have continued if the curve at the aneurysm's origin had not been present. Aneurysms at the PICA-vertebral junction usualthese lesions are determined by the course of the vertebral artery and PICA; that is, they occur at branching sites and at curves in the parent vessel, and point in the direction in which flow would have continued if the curve at the aneurysm's origin had not been present. Aneurysms at the PICA-vertebral junction usually occur at least 1 cm above the foramen magnum level, arise distal to the PICA origin in the angle between the two vessels, and are best approached by a paramedian incision with the patient in the lateral recumbent position. Isolated clipping of the aneurysm neck is essential in this instance, as trapping may compromise vital perforating arteries of the brain stem. More distal (retromedullary) PICA aneurysms are sometimes associated with another vascular anomaly (two cases in this series), and are best handled through a bilateral suboccipital craniectomy. Clipping of the neck is the preferred treatment, but trapping is usually safe, if necessary.

The lesion quotient appears to reliably identify pure radiation necrosis on standard sequence MRI. Other examined radiographic features, including arteriovenous shunting, gyriform lesion/edema distribution, enhancement pattern, and cyst formation, achieved 80% or greater predictive value but had either low sensitivity or low specificity.